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SummaryThe purpose of this study was to determine whether ␥ -aminobutyric acid (GABA) affects the rate of brain protein synthesis in ovariectomized female rats. Experiments were done on two groups of 24-wk-old ovariectomized female rats given 0 or 0.5% GABA added to the 20% casein diet. The concentrations of plasma growth hormone (GH) increased significantly with the 20% casein ϩ 0.5% GABA compared with the 20% casein diet alone. In the brain regions, GABA treatment to the basal diet elevated significantly the fractional and absolute rates of protein synthesis. In brain regions, the RNA activity [g protein synthesized/(g RNA·d)] significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was not related to the fractional rate of protein synthesis. The results suggest that the administration of GABA to ovariectomized female rats is likely to increase the concentrations of plasma GH and the rate of protein synthesis in the brain, and that RNA activity is at least partly related to the fractional rate of brain protein synthesis. Key Words ␥ -aminobutyric acid, growth hormone, protein synthesis, brain, ratsThe metabolic response to dietary proteins, age and hormonal factors includes marked changes in protein synthesis, especially in liver, muscle and intestine ( 1 -5 ). Protein synthesis in the brain is also sensitive to the alteration of dietary amino acid composition in young rats ( 6 , 7 ).Many investigators have reported that protein synthesis declined in specific tissues (e.g., liver or muscle) and in the whole body throughout development in mammals after weaning ( 8 -10 ). We demonstrated that the rate of protein synthesis in the brain decreased with age in rats after weaning ( 11 ).In many investigations, not only age but also sex hormone deficiency has been shown to affect body composition and function in postmenopausal women ( 12 ). Estrogen increases tissue protein synthesis by stimulating transcriptional activity ( 13 , 14 ). We also reported that estrogen increased protein synthesis in the brain of ovariectomized female rats ( 15 ). On the other hand, several investigators demonstrated that estrogen stimulated the release of ␥ -aminobutyric acid (GABA) in the brain ( 16 ). GABA is a kind of the amino acid widely distributed in nature, and is an inhibitory transmitter compound in vertebrates ( 17 , 18 ). Recently, GABA has been attracting attention as a food with functions such as improvement of memory and study capability, bloodpressure lowering action and relaxation ( 16 , 19 ). In a previous study, we reported that the administration of GABA to young male rats increased the concentration of plasma growth hormone (GH) and the rate of protein synthesis in the brain, and resulted in a positive correlation between the rate of protein synthesis in the brain and the plasma concentration of GH ( 20 ). GH is well known as an anabolic hormone in protein metabolism. Ohsumi et al. ( 21 ) demonstrated that hypopysectomy has been shown to decrease the rate of pr...

SummaryThe purpose of this study was to determine whether the growth hormone (GH) affects the rate of brain protein synthesis in hypophysectomized aged rats. Experiments were conducted on three groups of 24-wk-old male rats: group 1 were hypophysectomized to reduce the level of plasma GH, group 2 were hypophysectomized and treated with GH and group 3 were sham-operated controls. The fractional rates of protein synthesis in the brains of hypophysectomized rats with GH were significantly greater than those in hypophysectomized rats without GH. In the cerebral cortex and cerebellum, the RNA activity [g protein synthesized/(g RNA·d)] significantly correlated with the fractional rate of protein synthesis ( r Ͼ 0.88, p Ͻ 0.001). The RNA concentration (mg RNA/ g protein) was also related to the fractional rate of protein synthesis in these organs ( r Ͼ 0.56, p Ͻ 0.05). The results suggest that the treatment of GH to hypophysectomized aged rats is likely to increase the rate of protein synthesis in the brain, and that RNA activity is at least partly related to the fractional rate of brain protein synthesis. Key Words growth hormone, hypophysectomy, protein synthesis, brain, ratsThe metabolic response to dietary proteins, age and hormonal factors includes marked changes in protein synthesis, especially in the liver, muscle and intestine ( 1-5 ). Protein synthesis in the brain is also sensitive to the alteration of dietary amino acid composition in young rats ( 6 , 7) .Many investigators have reported that protein synthesis declined in specific tissues (e.g., liver or muscle) and in the whole body throughout development in mammals after weaning (8)(9)(10). We demonstrated that the rate of protein synthesis in the brain decreased with age in rats after weaning ( 11 ) . In many investigations, the protein synthesis in the brain and the concentration of plasma growth hormone (GH) has been shown to depend on the quantity and quality of dietary protein in aged rats (12)(13)(14). GH has been known to increase tissue protein synthesis by stimulating translational activity ( 15 ). However, the role of GH in maintaining the rate of brain protein synthesis remains unknown under physiological conditions.Recently, several investigators demonstrated that there were GH receptors in brain regions, and that GH had a direct affect on brain function (e.g., gene expression in neurons and memory) ( 16 ). The possibility that the hormone itself may pass the blood-brain barrier is supported by several studies ( 17 ). Therefore, the possible effects of GH on brain protein synthesis in hypophysectomized aged rats are of nutritional importance in understanding the role of protein nutrition in the brain function in mammals.The purpose of our study was to determine whether the regulation of brain protein synthesis in aged rats was mediated through changes in the concentration of GH when the quantity and quality of dietary protein is manipulated. Thus, in the present study, the effect of GH treatment on the rates of brain protein synthesis were dete...

SummaryThe purpose of this study was to determine whether the regulation of brain protein synthesis was mediated through changes in the plasma concentration of growth hormone (GH) when dietary ␥ -aminobutyric acid (GABA) treatment was manipulated in hypophysectomized or sham-operated aged rats. Experiments were done on four groups of hypophysectomized and sham-operated (24-wk-old) male rats given 0% or 0.5% GABA added to a 20% casein diet. The concentrations of plasma GH and fractional rates of protein synthesis in the brains increased significantly with the 20% casein ϩ 0.5% GABA compared with the 20% casein diet alone in the sham-operated rats. However GABA treatment to the basal diet did not affect the rates of protein synthesis in the hypophysectomized rats. In the cerebral cortex and cerebellum, the RNA activity [g protein synthesized/(g RNA·d)] significantly correlated with the fractional rate of protein synthesis. The RNA concentration (mg RNA/g protein) was also related to the fractional rate of protein synthesis in these organs. The results suggest that treatment with GABA is likely to increase the concentrations of GH and the rate of brain protein synthesis in sham-operated rats only, not in hypophysectomized rats, and that the GABA-induced increase in the concentration of GH may be primarily responsible for changes in the brain protein synthesis. The RNA activity is at least partly related to the fractional rate of brain protein synthesis. Key Words ␥ -aminobutyric acid, growth hormone, protein synthesis, brain, ratsThe metabolic response to dietary proteins, age and hormonal factors includes marked changes in protein synthesis, especially in the liver, muscles and intestines ( 1-5 ). Protein synthesis in the brain is also sensitive to the alteration of dietary amino acid composition in young rats ( 6 , 7 ).Many investigators have reported that protein synthesis declines in specific tissues (e.g., liver or muscle) and in the whole body throughout development in mammals after weaning ( 8-10 ). We demonstrated that the rate of protein synthesis in the brain decreases with age in rats after weaning ( 11 ). In many investigations, not only age but also growth hormone (GH) deficiency has been shown to affect many functions related to the central nervous system in mammals ( 12 ). GH is well known as the anabolic hormone in protein metabolism. Several investigators have demonstrated that the protein synthesis in visceral organs, skeletal muscle and brains was increased by GH in rats ( 13 , 14 ).␥ -Aminobutyric acid (GABA) is a kind of amino acid widely distributed over the nature, and is an inhibitory transmitter compound in vertebrates ( 15 , 16 ). Recently, GABA was attracted attention as a functional food for improvement in memory and study capability, bloodpressure reduction and relaxation inducement ( 17 , 18 ). In a previous study, we reported that administration of GABA to young and aged rats increased the concentration of plasma GH and the rate of protein synthesis in the brain, and that a positive c...

The purpose of the present study was to determine whether the regulation of brain protein synthesis was mediated through changes in the plasma concentrations of insulin and growth hormone (GH), and whether the concentrations of amino acids in the brain and plasma regulate the brain protein synthesis when the quantity and quality of dietary protein is manipulated. Two experiments were done on three groups of aged rats given diets containing 20% casein, 5% casein or 0% casein (Experiment 1), and 20% casein, 20% gluten, or 20% gelatin (Experiment 2) for 1 d (only one 5-h period) after all rats were fed the 20% casein diet for 10 d (only 5-h feeding per day). The aggregation of brain ribosomes, the concentration in plasma GH, and the branched chain amino acids in the plasma and cerebral cortex declined with a decrease of quantity and quality of dietary protein. The concentration of plasma insulin did not differ among groups. The results suggest that the ingestion of a higher quantity and quality of dietary protein increases the concentrations of GH and several amino acids in aged rats, and that the concentrations of GH and amino acids are at least partly related to the mechanism by which the dietary protein affects brain protein synthesis in aged rats.

SummaryWe have shown that urinary urea excretion increased in rats given a lower quality protein. The purpose of present study was to determine whether the composition of dietary amino acids affects urea synthesis. Experiments were done on three groups of rats given diets containing a 10% gluten amino acid mix diet or 10% casein amino acid mix diet or 10% whole egg protein amino acids mix diet for 10 d. The urinary excretion of urea, the liver concentration of N -acetylglutamate, and the liver concentration of free serine, glutamic acids and alanine were greater in the group given the amino acid mix diet of lower quality. The fractional and absolute rates of protein synthesis in tissues declined with a decrease in quality of dietary amino acids. The hepatic concentration of ornithine and the activities of hepatic urea-cycle enzymes were not related to the urea excretion. These results suggest that the increased concentrations of amino acids and N -acetylglutamate seen in the liver of rats given the amino acid mix diets of lower quality are likely among the factors stimulating urea synthesis. The protein synthesis in tissues is at least partly related to hepatic concentrations of amino acids. The composition of dietary amino acids is likely to be one of the factors regulating urea synthesis when the quality of dietary protein is manipulated.

SummaryWe have shown that the rate of brain protein synthesis in aged rats depended on the quality and quantity of dietary protein consumed. The purpose of this study was to determine whether the quality and quantity of dietary protein affected the phosphorylation of eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and ribosomal protein S6 kinase (S6K1) and regulated the brain protein synthesis. Two experiments were done on three groups of 24-wk-old male rats given diets containing 20% casein, 20% gluten, or 20% gelatin (Experiment 1), and 20% casein, 5% casein or 0% casein (Experiment 2) for 10 d. The phosphorylation of S6K1 in both the cerebral cortex and cerebellum, and the phosphorylation of 4E-BP1 in the cerebral cortex declined with a decrease of quality and quantity of dietary protein. The phosphorylation of 4E-BP1 in the cerebellum did not differ among groups. The results suggest that the ingestion of a higher quality and quantity of dietary protein stimulates the phosphorylation of 4E-BP1 and S6K1 in the brain and increases the brain protein synthesis in the aged rats. Key Words dietary protein, 4E-BP1, S6K1, protein synthesis, brainThe metabolic response to dietary proteins, age and hormonal factors includes marked changes in protein synthesis, especially in the liver, muscles and intestine ( 1-5 ). Protein synthesis in the brain is also sensitive to the alteration of dietary amino acid composition in young rats ( 6 , 7 ).Many investigators have reported that protein synthesis declined in specific tissues (e.g., liver or muscle) and in the whole body throughout development in mammals after weaning (8)(9)(10). We demonstrated that the rate of protein synthesis in the brain decreased with age in rats after weaning ( 11 ). In many investigations, the protein synthesis and the concentrations of branched-chain amino acids in the brain have been shown to depend on the quality and quantity of dietary protein in aged rats (12)(13)(14).In both liver ( 15 ) and skeletal muscle ( 16 ), the stimulation of protein synthesis caused by amino acids and protein was reported to be mediated by an increase in the initiation of mRNA translation. Administration of leucine in vivo enhanced muscle protein synthesis through the activation of the binding of mRNA to the 40S ribosomal subunit ( 17 ). The mRNA binding step is regulated by initiation factors collectively referred to as eIF4F ( 18 ). The eIF4F initiation factors include eIF4E, eIF4A, eIF4G and eIF3. The most studied example of the regulation of protein synthesis occurring at the mRNA binding step is the reversible sequestration of eIF4E into an inactive complex with the eIF4E binding protein, 4E-BP1. The binding site on eIF4E for 4E-BP1 overlaps with the eIF4G binding site. Thus, the binding of eIF4E to 4E-BP1 precludes the binding of the eIF4E-mRNA complex to the 40S ribosomal subunit ( 19 ). The interaction between eIF4E and 4E-BP1 is regulated by phosphorylation of 4E-BP1; specifically hyperphosphorylation prevents the binding while hypophosphoryl...

The brain protein synthesis is sensitive to the dietary protein; however, the role of dietary protein on biomarkers including choline acetyltransferase and nerve growth factor (NGF) for the function of cholinergic neurons remains unknown in young rats. The purpose of this study was to determine whether the quantity and quality of dietary protein affects the concentration of NGF and activity of choline acetyltransferase, and their mRNA levels in the brains of young rats. Experiments were carried out on five groups of young rats (4 weeks) given the diets containing 0, 5, 20% casein, 20% gluten or 20% gelatin for 10 days. The activity of choline acetyltransferase in the cerebral cortex and hippocampus declined gradually with a decrease in quantity and quality of dietary protein. The concentration of NGF in the cerebral cortex and the mRNA levels of choline acetyltransferase in the cerebral cortex and hippocampus did not differ among groups. However, the concentration and mRNA level of NGF in the hippocampus was significantly lower in rats fed with lower quantity of protein or lower quality of protein. In the hippocampus, the mRNA levels of NGF significantly correlated with the NGF concentration when the quantity (r = 0.704, P < 0.01) and quality (r = 0.682, P < 0.01) of dietary protein was manipulated. It was further found that a significant positive correlation existed between the NGF concentration and the activity of choline acetyltransferase in the hippocampus (dietary protein quantity, r = 0.632, P < 0.05; dietary protein quality, r = 0.623, P < 0.05). These results suggest that the ingestion of lower quantity and quality of dietary protein are likely to control the mRNA level and concentration of NGF, and cause a decline in the activity of choline acetyltransferase in the brains of young rats.